Lapidot T, Kollet O
Dept of Immunology, The Weizmann Institute of Science, Rehovot 76100, Israel.
Leukemia. 2002 Oct;16(10):1992-2003. doi: 10.1038/sj.leu.2402684.
Hematopoietic stem cells are identified based on their functional ability to migrate via the blood circulation of transplanted recipients, to home to the host bone marrow and to durably repopulate this organ with high levels of maturing myeloid and lymphoid cells. While a small pool of undifferentiated stem cells with the potential to repeat the entire process in serially transplanted recipients is maintained within the bone marrow, maturing cells are continuously released into the circulation. In recent years pre-clinical, functional in vivo models for human stem cells have been developed, using immune-deficient mice or pre-immune, fetal sheep as recipients. The mechanism of human stem cell migration, homing and repopulation in transplanted immune-deficient NOD/SCID and NOD/SCID/B2m(null) mice as well as the accessory mediators that facilitate these processes, will be reviewed. In particular, the essential roles of the chemokine SDF-1 and its receptor CXCR4 which mediate and regulate stem cell homing and repopulation will be discussed.
造血干细胞是根据其功能能力来识别的,这些功能包括通过移植受体的血液循环迁移、归巢到宿主骨髓以及用高水平的成熟髓系和淋巴细胞持久地重新填充该器官。虽然在骨髓中维持着一小部分未分化的干细胞池,它们有可能在连续移植的受体中重复整个过程,但成熟细胞会不断释放到循环中。近年来,已经开发出了针对人类干细胞的临床前体内功能模型,使用免疫缺陷小鼠或未免疫的胎羊作为受体。本文将综述人类干细胞在移植的免疫缺陷NOD/SCID和NOD/SCID/B2m(缺失)小鼠中的迁移、归巢和重新填充机制,以及促进这些过程的辅助介质。特别地,将讨论趋化因子SDF-1及其受体CXCR4在介导和调节干细胞归巢和重新填充中的重要作用。